{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:31:12Z","timestamp":1789986672817,"version":"4.0.1"},"reference-count":48,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2018,7,20]],"date-time":"2018-07-20T00:00:00Z","timestamp":1532044800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,7,20]],"date-time":"2018-07-20T00:00:00Z","timestamp":1532044800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,7,20]],"date-time":"2018-07-20T00:00:00Z","timestamp":1532044800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000888","name":"W. M. Keck Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000888","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01NS057819"],"award-info":[{"award-number":["5R01NS057819"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007857","name":"Intellectual and Developmental Disabilities Research Center","doi-asserted-by":"publisher","award":["1U54HD083092"],"award-info":[{"award-number":["1U54HD083092"]}],"id":[{"id":"10.13039\/100007857","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000893","name":"Simons Foundation","doi-asserted-by":"publisher","award":["273886"],"award-info":[{"award-number":["273886"]}],"id":[{"id":"10.13039\/100000893","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>The Mecp2+\/- mouse model recapitulates many phenotypes of patients with Rett syndrome (RTT), including learning and memory deficits. It is unknown, however, how the disease state alters memory circuit functions in vivo in RTT mice. Here we recorded from hippocampal place cells, which are thought to encode spatial memories, in freely moving RTT mice and littermate controls. We found that place cells in RTT mice are impaired in their experience-dependent increase of spatial information. This impairment is accompanied by an enhanced baseline firing synchrony of place cells within ripple oscillations during rest, which consequently occludes the increase in synchrony after a novel experience. Behaviorally, contextual memory is normal at short but not long time scale in RTT mice. Our results suggest that hypersynchrony interferes with memory consolidation and leads to impaired spatial memory codes in RTT mice, providing a possible circuit mechanism for memory deficits in Rett Syndrome.<\/jats:p>","DOI":"10.7554\/elife.31451","type":"journal-article","created":{"date-parts":[[2018,7,20]],"date-time":"2018-07-20T11:00:22Z","timestamp":1532084422000},"source":"Crossref","is-referenced-by-count":28,"title":["Impaired spatial memory codes in a mouse model of Rett syndrome"],"prefix":"10.7554","volume":"7","author":[{"given":"Sara E","family":"Kee","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States"},{"name":"Department of Neuroscience, Baylor College of Medicine, Houston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8579-7316","authenticated-orcid":true,"given":"Xiang","family":"Mou","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0700-3349","authenticated-orcid":true,"given":"Huda Y","family":"Zoghbi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Baylor College of Medicine, Houston, United States"},{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States"},{"name":"Department of Neurology, Baylor College of Medicine, Houston, United States"},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, United States"},{"name":"Howard Hughes Medical Institute, Baylor College of Medicine, Houston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4115-5888","authenticated-orcid":true,"given":"Daoyun","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States"},{"name":"Department of Neuroscience, Baylor College of Medicine, Houston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2018,7,20]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/13810","article-title":"Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2","volume":"23","author":"Amir","year":"1999","journal-title":"Nature Genetics"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1126\/science.1589772","article-title":"High-frequency network oscillation in the Hippocampus","volume":"256","author":"Buzs\u00e1ki","year":"1992","journal-title":"Science"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1016\/0306-4522(89)90423-5","article-title":"Two-stage model of memory trace formation: a role for\u00a0\u2018noisy\u2019\u00a0brain states","volume":"31","author":"Buzs\u00e1ki","year":"1989","journal-title":"Neuroscience"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"7854","DOI":"10.1523\/JNEUROSCI.1704-07.2007","article-title":"Experience-dependent increase in CA1 place cell spatial information, but not spatial reproducibility, is dependent on the autophosphorylation of the alpha-isoform of the calcium\/calmodulin-dependent protein kinase II","volume":"27","author":"Cacucci","year":"2007","journal-title":"Journal of Neuroscience"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.neuron.2007.10.001","article-title":"The story of Rett syndrome: from clinic to neurobiology","volume":"56","author":"Chahrour","year":"2007","journal-title":"Neuron"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"8118","DOI":"10.1523\/JNEUROSCI.3130-14.2015","article-title":"Progressive functional impairments of hippocampal neurons in a tauopathy mouse model","volume":"35","author":"Ciupek","year":"2015","journal-title":"Journal of Neuroscience"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"e00647","DOI":"10.7554\/eLife.00647","article-title":"Rigid firing sequences undermine spatial memory codes in a neurodegenerative mouse model","volume":"2","author":"Cheng","year":"2013","journal-title":"eLife"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/S0896-6273(00)00135-5","article-title":"Ensemble patterns of hippocampal CA3-CA1 neurons during sharp wave-associated population events","volume":"28","author":"Csicsvari","year":"2000","journal-title":"Neuron"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"14984","DOI":"10.1523\/JNEUROSCI.1091-14.2014","article-title":"Millisecond timescale synchrony among hippocampal neurons","volume":"34","author":"Diba","year":"2014","journal-title":"Journal of Neuroscience"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1038\/nrn2762","article-title":"The memory function of sleep","volume":"11","author":"Diekelmann","year":"2010","journal-title":"Nature Reviews Neuroscience"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1016\/0887-8994(88)90081-1","article-title":"EEG abnormalities aid diagnosis of rett syndrome","volume":"4","author":"Garofalo","year":"1988","journal-title":"Pediatric Neurology"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/hipo.20707","article-title":"Disruption of ripple-associated hippocampal activity during rest impairs spatial learning in the rat","volume":"20","author":"Ego-Stengel","year":"2010","journal-title":"Hippocampus"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/S0166-4328(99)00186-2","article-title":"Contextual fear, gestalt memories, and the hippocampus","volume":"110","author":"Fanselow","year":"2000","journal-title":"Behavioural Brain Research"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"7681","DOI":"10.1523\/JNEUROSCI.1958-04.2004","article-title":"Hippocampal plasticity across multiple days of exposure to novel environments","volume":"24","author":"Frank","year":"2004","journal-title":"Journal of Neuroscience"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1038\/nn.2384","article-title":"Selective suppression of hippocampal ripples impairs spatial memory","volume":"12","author":"Girardeau","year":"2009","journal-title":"Nature Neuroscience"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1177\/08830738050200090801","article-title":"Neurophysiology of Rett syndrome","volume":"20","author":"Glaze","year":"2005","journal-title":"Journal of Child Neurology"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1038\/85899","article-title":"A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome","volume":"27","author":"Guy","year":"2001","journal-title":"Nature Genetics"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1038\/nature15694","article-title":"Forniceal deep brain stimulation rescues hippocampal memory in Rett syndrome mice","volume":"526","author":"Hao","year":"2015","journal-title":"Nature"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1038\/nn1825","article-title":"Coordinated memory replay in the visual cortex and Hippocampus during sleep","volume":"10","author":"Ji","year":"2007","journal-title":"Nature Neuroscience"},{"key":"bib20","article-title":"DataManager","volume-title":"Github","author":"Ji","year":"2018","unstructured":"Ji D. 2018. DataManager. Github. f64fcdd. https:\/\/github.com\/DaoyunJiLab\/DataManager."},{"key":"bib21","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1152\/physrev.00021.2010","article-title":"Framing spatial cognition: neural representations of proximal and distal frames of reference and their roles in navigation","volume":"91","author":"Knierim","year":"2011","journal-title":"Physiological Reviews"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"e0164675","DOI":"10.1371\/journal.pone.0164675","article-title":"Optogenetically blocking sharp wave ripple events in sleep does not interfere with the formation of stable spatial representation in the CA1 area of the Hippocampus","volume":"11","author":"Kov\u00e1cs","year":"2016","journal-title":"PLoS\u00a0One"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1016\/S0896-6273(02)01096-6","article-title":"Memory of sequential experience in the hippocampus during slow wave sleep","volume":"36","author":"Lee","year":"2002","journal-title":"Neuron"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1038\/416090a","article-title":"Long-term plasticity in hippocampal place-cell representation of environmental geometry","volume":"416","author":"Lever","year":"2002","journal-title":"Nature"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/j.neuron.2016.07.018","article-title":"Loss and gain of MeCP2 cause similar hippocampal circuit dysfunction that is rescued by deep brain stimulation in a rett syndrome mouse model","volume":"91","author":"Lu","year":"2016","journal-title":"Neuron"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1038\/nature00807","article-title":"Role of experience and oscillations in transforming a rate code into a temporal code","volume":"417","author":"Mehta","year":"2002","journal-title":"Nature"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1038\/297681a0","article-title":"Place navigation impaired in rats with hippocampal lesions","volume":"297","author":"Morris","year":"1982","journal-title":"Nature"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"S62","DOI":"10.1016\/S0387-7604(01)00381-3","article-title":"Neuroimaging studies in Rett syndrome","volume":"23","author":"Naidu","year":"2001","journal-title":"Brain and Development"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1038\/381425a0","article-title":"Geometric determinants of the place fields of hippocampal neurons","volume":"381","author":"O'Keefe","year":"1996","journal-title":"Nature"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/0006-8993(71)90358-1","article-title":"The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat","volume":"34","author":"O'Keefe","year":"1971","journal-title":"Brain Research"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1002\/hipo.450030307","article-title":"Phase relationship between hippocampal place units and the EEG theta rhythm","volume":"3","author":"O'Keefe","year":"1993","journal-title":"Hippocampus"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1037\/0735-7044.106.2.274","article-title":"Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning","volume":"106","author":"Phillips","year":"1992","journal-title":"Behavioral Neuroscience"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1126\/science.1232655","article-title":"Multisensory control of hippocampal spatiotemporal selectivity","volume":"340","author":"Ravassard","year":"2013","journal-title":"Science"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1038\/nn.4543","article-title":"Sharp wave ripples during learning stabilize the hippocampal spatial map","volume":"20","author":"Roux","year":"2017","journal-title":"Nature Neuroscience"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1093\/hmg\/dds406","article-title":"Female Mecp2(+\/-) mice display robust behavioral deficits on two different genetic backgrounds providing a framework for pre-clinical studies","volume":"22","author":"Samaco","year":"2013","journal-title":"Human Molecular Genetics"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"2065","DOI":"10.1073\/pnas.0437938100","article-title":"Communication between neocortex and hippocampus during sleep in rodents","volume":"100","author":"Sirota","year":"2003","journal-title":"PNAS"},{"key":"bib37","first-page":"1030","volume-title":"Advances in Neural Information Processing Systems","author":"Skaggs","year":"1993"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"1870","DOI":"10.1126\/science.271.5257.1870","article-title":"Replay of neuronal firing sequences in rat hippocampus during sleep following spatial experience","volume":"271","author":"Skaggs","year":"1996","journal-title":"Science"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1016\/j.neuron.2013.09.014","article-title":"Impaired hippocampal ripple-associated replay in a mouse model of schizophrenia","volume":"80","author":"Suh","year":"2013","journal-title":"Neuron"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1126\/science.1148979","article-title":"Fast-forward playback of recent memory sequences in prefrontal cortex during sleep","volume":"318","author":"Tatsuno","year":"2007","journal-title":"Science"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1016\/j.neuron.2017.05.024","article-title":"Temporal and rate coding for discrete event sequences in the Hippocampus","volume":"94","author":"Terada","year":"2017","journal-title":"Neuron"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/0006-8993(90)90555-P","article-title":"Long-term stability of the place-field activity of single units recorded from the dorsal hippocampus of freely behaving rats","volume":"509","author":"Thompson","year":"1990","journal-title":"Brain Research"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1016\/j.neuron.2016.10.020","article-title":"Hippocampal offline reactivation consolidates recently formed cell assembly patterns during sharp Wave-Ripples","volume":"92","author":"van de Ven","year":"2016","journal-title":"Neuron"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.neuron.2004.08.031","article-title":"Sleep-dependent learning and memory consolidation","volume":"44","author":"Walker","year":"2004","journal-title":"Neuron"},{"key":"bib45","article-title":"XClust","volume-title":"Github","author":"Wilson","year":"2008","unstructured":"Wilson M. 2008. XClust. Github. https:\/\/github.com\/wilsonlab\/mwsoft64\/tree\/master\/src\/xclust."},{"key":"bib46","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1126\/science.8351520","article-title":"Dynamics of the hippocampal ensemble code for space","volume":"261","author":"Wilson","year":"1993","journal-title":"Science"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1126\/science.8036517","article-title":"Reactivation of hippocampal ensemble memories during sleep","volume":"265","author":"Wilson","year":"1994","journal-title":"Science"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1038\/nn.4507","article-title":"Hippocampal awake replay in fear memory retrieval","volume":"20","author":"Wu","year":"2017","journal-title":"Nature Neuroscience"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/31451\/elife-31451-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/31451\/elife-31451-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/31451","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T20:48:37Z","timestamp":1697057317000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/31451"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,20]]},"references-count":48,"alternative-id":["10.7554\/eLife.31451"],"URL":"https:\/\/doi.org\/10.7554\/elife.31451","archive":["CLOCKSS"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.5061\/dryad.h752n4q","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.31451.022","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.31451.021","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,20]]},"article-number":"e31451"}}